Tobacco use is one of the most significant public health issues facing our nation and the world today. Although tobacco use has declined over the past three decades, this decline has begun to level off and the remain smokers appear to have more difficulty quitting. Individuals with psychiatric comorbidity, including depression and alcohol use, as well as women find it more difficult to successful quit. In addition, adolescent smoking is on the rise and current treatments are ineffective for this important group of smokers. The goal of this center is to investigate and improve the treatment of tobacco dependence using transdisciplinary approaches to 1) understand the underlying factors associated with failure to enter treatment and poor treatment outcome, and 2) to develop and evaluate novel behavioral and pharmacological treatments that address these factors. The following specific aims will be achieved by the TTURC: 1) To galvanize research interest across different disciplines that will address the problem of tobacco dependence in these high risk groups. The theories and methods of each discipline will be brought to bear on the critical issues and the results will be synthesized at a level that transcends disciplinary boundaries. 2) To provide career development activities for graduate students, medical students, and junior investigators from different disciplines that will expose them to research on tobacco use and dependence and will potentially influence some to pursue careers studying issues related to tobacco. 3) To provide a mechanism to rapidly review and fund pilot projects that have significant promise for advancing the field. 4) To conduct a series of programmatic research studies aimed at understanding risk factors for treatment failure and developing more efficacious treatments.